The film opens with a recap of the zombie outbreak during the credits, and we are brought to the time setting of today. In a small, run-down town, zombies are everywhere, and they seem to retain knowledge of their lives before they died. Some zombies try to play instruments in a town square. A teenage boy zombie holds hands with a female teenage zombie as if on a date. The teenage zombies walk past a gas station, where the zombie attendant hears the bell that signifies that someone is there. The zombie walks outside and is ready to fill a car with gas, but he sees that there is no car so he puts back the gas nozzle.
From the name-tag that he has, his name is Big Daddy (Eugene Clark). Watching Big Daddy through binoculars is Riley (Simon Baker) and his new rookie. Riley sees that the zombies are getting somewhat smarter, and that they are thinking more. This worries him. Riley is a part of a group of humans who venture out to small towns and gather essential supplies for people back at the last known human city. Riley built a vehicle that is justly named 'Dead Reckoning', which is basically a combination of a bus, train, and tank. It is fully loaded with machine guns, rockets, and fireworks.
Riley and the rookie meet up with Cholo (John Leguizamo), who also has the same job as Riley of collecting supplies as well as dumping trash in a nearby landfill. Riley tells Cholo that the zombies are thinking, and to be careful when they go into the town. Cholo brushes off the warning, but Riley gets his point across. It is Riley's last night out, and he doesn't want anyone dying. Cholo reveals that it is his last night out as well. A figure is walking towards Riley and the rookie, but they don't see it. The rookie turns around, sees it, and gets ready to blast it to hell when Riley recognizes it and orders the rookie to lower his weapon.
It is only Charlie (Robert Joy), a man who has half of his face burnt from a fire. Charlie is slightly retarded. He is Riley's right-hand man, and is his trusted friend. Charlie and Riley wonder how Cholo is retiring tonight, unless he won the lottery. The rag-tag team of humans get in their jeeps and motorcycles, and proceed towards the town. Pretty Boy (Joanne Boland), the female operator of Dead Reckoning, fires off some fireworks over the town. All the zombies stare at the sky, their attentions focused on the lights. This allows Riley and the humans to move freely throughout the town unnoticed.
Big Daddy is the only zombie who does not look at the fireworks. He sees his fellow undead companions looking at the sky, and he tries to shake their attention from it. The humans are just about finished with finding things to bring back home when Cholo tells Riley that he just needs to make one more stop at a store. Cholo really is going to the shop to steal alcohol, which sells well on the streets back home. Riley urges him not to go, but Cholo ignores him. He takes the rookie and Foxy (Tony Nappo). There's something wrong: the fireworks are jammed. The zombies are starting to become aware of the humans in their midst, and start to stumble towards them.
Riley orders Dead Reckoning and the rest of his team to evacuate and retreat back home. Riley and Charlie will go and bring back Cholo with his men. Dead Reckoning starts to head out and blasts away many zombies with its machine guns. Big Daddy sees the danger of the guns and tries to get the other zombies to take cover, but they are not getting it. He holds onto a zombie's head and tries to push him towards the ground, but the machine gun fire blasts the zombie's head off. Big Daddy, still holding onto the zombie's head, sees that it is still alive. To put it out of its misery, he drops the head and stomps on it, crushes its brains. Big Daddy roars with rage.
Back at the shop, while looking for some quality alcohol, Cholo is jumped by a zombie. Foxy and the rookie can't get a clean shot, but Cholo prevails safely when he pulls his spear gun from his leg and blasts the zombie's brains out. He collects the alcohol and stops at the counter. He empties a box and tells the rookie to collect it. Some of it falls behind the counter. Cholo and Foxy wait outside. The rookie reaches over the counter and a security guard zombie bites a chunk out of his hand. The rookie screams in pain and stumbles outside. Riley and Charlie pull up to the store and see what's happening. Riley blasts the zombie's brains out. Cholo orders Riley to step aside, as the rookie is going to become one of them.
While Riley argues about the rookie's fate, the rookie snatches Riley's pistol and blows his own brains out. This is not how Riley wanted to start his retirement. Riley, Charlie, Cholo, and Foxy go back to the city. Before one of the bikers leaves, Big Daddy tries to grab him but instead grabs his machine gun. Big Daddy doesn't know what to do with it, but slings it over his shoulder and starts to walk in the direction that Dead Reckoning left. The other zombies, including a butcher zombie (Boyd Banks), a tambourine-playing zombie from the town sqare (Jasmin Geljo), a blond female athlete zombie wearing a woman's red softball uniform (Jennifer Baxter) with the number 9 printed on it, as well as the zombie teenage couple and several others, follow Big Daddy.
Arriving back at their base that has an underground tunnel leading under a river to the fortified city, Cholo and Foxy watch a commercial for Fiddler's Green, an upper-class community that resides on a hill overlooking the city. It has its own mall, bank, and restaurants with tuxedo-clad waiters. The wealthy live there, and everyone else lives in the streets below. The city is fortified with electrified fences and soldiers staying on guard. At the barrier, a stray zombie tries to climb the fence, but is electrocuted and shot to pieces. The city is surrounded by water on all sides, and the main way to get into the city is called The Throat, which is a bridge.
Fiddler's Green is where Cholo wants to retire, and he is confident Kaufman (Dennis Hopper), the owner and manager, will allow him to enter. Riley confronts Cholo about the rookie's death, but Cholo tells him that is the price they pay, and they all knew the risks that came with the job. Cholo takes the finest alcohol he stole and starts to head on over to Fiddler's Green. Riley and Charlie give antibiotics to a homeless man's son, and they head on over to a garage. Riley invested his money in a car, and he was going to drive away to a place with less people, somewhere north like Canada. But, his car is gone and he is not happy about it. Riley and Charlie head off to meet Chihuahua (Phil Fondacaro), who had promised Riley the car.
Cholo goes through Fiddler's Green's lavish mall and eventually makes his way to Kaufman's office on the top floor of the building. He pours some champagne into glasses and gives one to Kaufman. Cholo tells him that he is going to retire with all the money Kaufman owes him. Kaufman, however, tells him that space is limited in Fiddler's Green. Cholo sees right through this statement and the millionaire tells him that only certain people are allowed to live there. Kaufman basically tells him that he is not good enough to live there, and sends in a security officer. Kaufman tells Cholo that they will talk again when Cholo is less excited and sends him away. He tells the security officer that he will no longer need Cholo's "services". He understands, and tries to kill Cholo in the stairway, but Cholo is smarter and knocks him out. This double-cross is the last straw for Cholo. He leaves.
Riley and Charlie go to Chihuahua's underground place, which basically is a Vegas-like joint where people can gamble and buy prostitutes. People can even take a picture with a zombie at a booth (the zombies at the picture booth are Simon Pegg and Edgar Wright of "Shaun of the Dead"). Chihuahua is a midget who acts tough but couldn't hold his own in a fight. Riley confronts him about his car, but he says that he'll find it soon. He signals one of his guards to keep an eye on Riley. Tonight is a new kind of betting: people bet on which zombie will win in a fight. One zombie is spray-painted black on his mouth while the other is spray-painted red. In order to make them fight, they throw in a prostitute named Slack (Asia Argento).
She tries desperately to fend off the ravenous zombies while the crowd of gamblers cheer for their zombie to win. Riley sees what's going on, sees that no one is going to help this poor woman, and shoots/kills the two zombies in the ring. The shots prompt panic and everyone rushes to get out. Chihuahua tries to leave too. Charlie pulls out his rifle, licks the barrel, aims carefully, and blasts his head open. One of Chihuahua's men tries to shoot Riley, but Slack kicks him out of the way and takes the bullet for him in her arm. Charlie kills the other man. The police arrive and demand to know what is going on. All that is left is Riley, Charlie, and Slack. Riley just tells them "someone shot the little man."
Meanwhile, Big Daddy and the zombies get to a blocked pathway. They don't know how to get in, but Big Daddy sees the Butcher still holding his meat cleaver. He signals for him to hit the board blocking them with the cleaver, and the Butcher does. He hits the board repeatedly until Big Daddy can look through it. A couple of zombies suddenly appear in front of the hole in the board, and Big Daddy sees that they are hung upside down. He looks around and sees other zombies hanging upside down and having targets wrapped around their bodies. Big Daddy sees his target for all the pain his fellow zombies have endured: Fiddler's Green.
Riley, Charlie and Slare are in the city jail. Charlie asks Slack why she was put in the cage with the zombies. She tells him that she wanted to become a soldier, but someone else thought she would be a better whore and put her on the street. Riley tells her that she didn't answer Charlie's question. Slack tells them that Kaufman runs everything in and around Fiddler's Green, from the betting to the prostitution. She tried to help out some people of whom Kaufman didn't think too highly, and so he sentenced her to the cage fight. Slack asks Riley what his story is, and he says that nothing bad happened to him. She says that the zombies happened to everyone, and that's bad. Riley is not one for conversation, so Slack just pulls out a joint from her boot and smokes it.
Cholo, Foxy, Pretty Boy, Mouse (Max McCabe), and several other people decide to steal Dead Reckoning and hold Fiddler's Green for ransom. They try to pass off old papers as current ones requesting them to take Dead Reckoning from the soldier's hands, but the soldier to whom they give the papers doesn't buy it. Cholo hears gunfire and takes out his gun, wondering what it is. The soldier says that it is nothing to worry about, and that it is only target practice. Meanwhile, two soldiers are wasting time and shooting at a giant inflatable person. The shooter is saying that he would shoot better if the other soldier wouldn't keep breathing down his neck.
The other soldier is confused, as he is not close to the soldier. He turns on the light behind him and searches the surrounding grounds. He doesn't see anything, but he hears something out there. Big Daddy suddenly appears with the horde of zombies and attack the two soldiers. Cholo hears the screams and asks if they're practicing screaming too. The alarm goes off and the soldiers leave Cholo and his crews unguarded. They take Dead Reckoning and see that Big Daddy and the zombies are knocking over an non-electric fence. Soldiers are blasting the zombies, but there are too many of them. They knock the fence down and feast upon the soldiers, tearing them apart.
The soldiers are getting slaughtered. Cholo and company take off in Dead Reckoning. Upon seeing the vehicle, Big Daddy remembers what it did to the other zombies and squeezes his machine gun in his hand. It fires into the ground. He then points the gun at Dead Reckoning and fires at it. He hits it, but some of his shots miss and blow up a propane tank. One of the zombies catches on fire, and Big Daddy shoots and kills him to put him out of his misery. Big Daddy sees Fiddler's Green across the body of water and starts to move towards the lake with the other zombies including Butcher, Number 9, Tambourine Man, and the zombie teen couple.
Cholo contacts Kaufman, who is a bit annoyed that he is still alive. Cholo tells Kaufman the deal: Kaufman will give him and his crew $5 million or he will blow Fiddler's Green apart using Dead Reckoning. He wants the money transported to the port. Kaufman has until midnight, which is a couple of hours away. Kaufman talks with another businessman, and tells him that he will not deal with terrorists. However, Dead Reckoning could destroy their lifestyle and community.
Kaufman has Riley pulled out of jail and brought to his office. He tells Riley that Cholo has taken Dead Reckoning and that he wants back his two million dollar vehicle. He charges Riley to bring it back; Cholo can be brought back dead or alive. Riley wants his friends to help him with this mission. Kaufman allows it. All Riley wants in return is a car and plenty of weapons to last him a long time. He is fully prepared to travel to Canada in hopes of less people and zombies. Kaufman agrees. While Riley and Kaufman are discussing their deal, Charlie and Slack are talking back in jail. Charlie tells Slack that he takes care of Riley. Slack asks him why. Charlie says that Riley pulled him out of the fire that scarred him, and that they have been friends ever since.
Cholo is working out in Dead Reckoning while talking to Foxy. Cholo justifies his actions by saying that unless he does something, he's going to end up like the poor bastard outside (it's a zombie with a lawn mower). Cholo stops working out, pulls out his spear gun, and shoots the zombie in the eye. Cholo then orders Mouse to go to the port and wait for Kaufman's boat. Mouse will then report back to Cholo if they are rich or not. Mouse gets off Dead Reckoning on his skateboard and goes to a boathouse on the port. He gets scared of the movement within the boathouse, but it turns out to be rats.
Riley, Slack, and Charlie are released from jail and are getting geared up with weapons from the army. A soldier offers Charlie a machine gun that fires 18 bullets per second, but Charlie says that he won't need that many and prefers his rifle. The soldier calls him a retard. Riley tells the soldier that he shouldn't make fun of him. Slack takes the machine gun happily. But, Kaufman doesn't completely trust Riley and his friends. In come three soldiers that will make sure Riley doesn't fail: a tough Latino named Manolete (Sasha Roiz), a wisecracking female solder nicknamed Motown (Krista Bridges), and a hulking eithnic Samoa soldier named Pillsbury (Pedro Miguel Arce).
They head to the army post where they can get a vehicle, but they find it in flames and in ruin from the previous massacre that took place when Cholo left. They search the nearby parts for keys for a jeep, with Riley and Manolete going off on their own while Charlie and everyone else hang around a jeep. Riley and Manolete come across a severed foot in an army boot in the supply room. It is dark except for Manolete's flashlight. They hear a dripping sound. Upon further searching, they find a couple of zombies feasting on dead bodies. Manolete is ready to blast them away with his machine gun, but Riley tells him that they should use their hand guns. Riley and Manolete blast the zombies away, and they encounter Brubaker, now a zombie, chewing on a femur bone. Riley blasts his brains out.
Outside, Motown decides to hotwire a jeep. Charlie licks his rifle, then aims at something lurking about. Slack asks him why he licks his gun, and he just says that it is to prevent the reflection from getting into his vision. Slack asks him how can he even see, seeing how his aiming eye is on the burnt side of his face. He points the rifle at her face. She gets scared and pulls her machine gun out, but Charlie was really aiming directly next to Slack and blasts a zombie square in the forehead.
She aims her machine gun at Charlie and pulls the trigger, but she was returning the favor by killing a zombie behind him. However, the shot was so close to Charlie that his ear starts to bleed (he complains that his shot didn't hurt her). Riley and Manolete meet up with the team at the jeep. Once they are all in the jeep, a decapitated zombie walks up to Manolete and freaks him out. The zombie is not decapitated, though; the head is hanging behind his back. The zombie snaps ! his head forward and bites Manolete's arm. Pillsbury kills the zombie and they drive off.
It turns out that Riley can track Dead Reckoning with a homing device he placed in its center. Riley also reveals that his little brother was bitten by a zombie. In under than an hour, he turned and Riley had to kill him. Slack tells him that he was lying when he said nothing bad happened to him. He says coldly "nothing bad happened to me. That happened to my brother". Slack turns around and kills Manolete, since he is going to die.
Meanwhile, Big Daddy and the zombies are at the lake, and they are all staring at the water. Big Daddy jumps in to give an example, and the zombies follow.
Slack is driving the jeep, and Riley tells her quickly to pull over. She does, and Charlie holds Pillsbury and Motown at gunpoint. Riley knows that Kaufman will probably not live up to their deal and probably paid off the three soldiers to kill him and his friends once they find Dead Reckoning. Riley tells them that once they find Dead Reckoning, he will do whatever he wants with it. If they have a problem, they will be killed. They continue to drive and locate Dead Reckoning. Meanwhile, Mouse informs Cholo that the money didn't make it. He then blasts away a zombie that tried to get into the boathouse. When he goes to inspect the body, he is overrun by zombies, including one dressed like a clown. They eat him.
Big Daddy and his clan cross the lake and head to the streets of the human city. The zombies first attack two girls who were making out, then they attack everyone. Note: Tom Savini makes a zombie cameo as his biker character from the original Dawn of the Dead and hacks apart many people with his machete. The zombies are using shovels, chains, guns, knives, and various other weapons (including their teeth) as means of dismembering people. It is total chaos in the streets below Fiddler's Green. The Butcher zombie attacks a soldier with his cleaver. The soldier has a grenade in his hand and pulls the safety pin out. The Butcher hacks off the soldier's hand (still holding the grenade), and the soldier falls onto his own hand.
The grenade explodes and blows the soldier in half. The female softball player zombie, Number 9, manages to grab an M-16 assault rifle from a scared soldier. She doesn't know what to do with it, and this gives the soldier some time to reach for his back-up weapon. Big Daddy comes by and shows Number 9 how to pull the trigger. He directs the machine gun from firing into the ground to firing into the soldier's crotch, then his belly, then his upper body. Number 9 reluctantly drops her softball bat, and now holds onto the rifle and opens fire on more humans until she runs out of ammuntion. The Tambourine zombie relunctantly drops his tambourine to take posession of a crowbar for use as a weapon against the humans.
Riley and his group find Dead Reckoning. Pillsbury punches Motown out, thus being trusted by Riley. Riley and Charlie walk out to Dead Reckoning alone while Pillsbury and Slack hide in the nearby bushes. Motown is left in the jeep, knocked out. Riley and Charlie eventually talk their way in into the vehicle but are held at gunpoint by Cholo and his men. Cholo pulls out his spear gun and holds it under Riley's chin. Pretty Boy gets ready to fire rockets at Fiddler's Green. Riley protests, mainly because even if they hit it dead on, the destruction will kill many innocent people in the streets below. Slack sees that they are in danger, and she gets ready to fire. Motown wakes up, grabs a gun, and runs to the vehicle. She gets jumped by a zombie, who bites and rips a chunk out of her neck.
Riley hears her screaming, sees Slack in the bushes, and pushes Cholo out of Dead Reckoning. Slack fires and hits Cholo in the stomach. She and Pillsbury then blow away Motown and the zombie that attacked her. Charlie gets his gun back and turns the tables on Cholo's crew. Kaufman sees and hears the explosions outside in the streets below and thinks that Dead Reckoning has fired upon the city. Riley tells him (via phone) that it's not Cholo. Kaufman then fills out a couple of bags with money and is getting ready to leave. One of the businessmen sees what Kaufman is doing. Kaufman tells him to get down because there is a zombie nearby. The guy gets on the floor without looking and Kaufman shoots him. There wasn't a zombie anywhere near them, and Kaufman along with his black servant head down towards the mall.
Riley allows Cholo to leave with Foxy, and gives them guns. Riley then takes over Cholo's crew and Pretty Boy turns Dead Reckoning towards the city to save the people. Cholo and Foxy start to walk away when they encounter a zombie. The zombie bites Cholo and he stabs it in the head with a knife. Cholo is now doomed and Foxy aims his shotgun at his head. "It's your call" he says. Cholo says "no" and "I've always wanted to know how the other side lives". They take the jeep that Riley used to get there and drive back to the city outskirts. Cholo has a score to settle with Kaufman. Cholo wishes Foxy the best of luck, and Foxy drives away without Cholo. He starts to walk towards Fiddler's Green.
Big Daddy and the zombies are at the mall's entrance. They can't get in. Big Daddy, who is now holding a jackhammer by this time, uses it to smash the windows of the mall's entrance. The zombies follow his example and they gain access to the mall. They tear apart the upper-class snobs in the mall. The shoppers trample over each other trying to avoid certain death. Big Daddy encounters Kaufman and his servant. Kaufman tells Big Daddy that he "has no right" and shoots him, but keeps missing his head and hitting him in the leg and shoulder. Big Daddy roars with anger and continues to pursue Kaufman, who has gone to the underground parking complex.
His servant unlocks the flashy car and then goes to open the garage door. While he is gone, Big Daddy sneaks up on the car and starts to smash it with his bare hands. The servant sees the zombie and runs away... in the opposite direction... with the car keys. Big Daddy sees the gas nozzle nearby, and starts to pour gasoline all over the car. He smashes the windshield with the nozzle and pours the gas inside of the car. Big Daddy then leaves. Also, some of the people who survived the attacks on the mall and on the streets are now running to the gates of the city. However, the gates are still electrocuted. Zombies are still following them, and they are trapped. They are doomed.
Meanwhile, Dead Reckoning is just outside of the city's main bridge, Deep Throat. Riley has to get off and open the gate, seeing how it is up. While he goes inside and pushes the button to lower the bridge, Dead Reckoning is bombarded with hordes of zombies. Zombies are scratching at the vehicle and breaking their fingers/fingernails. One of the undead lunges for Riley and causes him to drop his gun. He yells out for Slack to kill it, but she's having her own problems with the zombies directly outside. Riley manages to decapitate the zombie using some controls from the bridge. Pretty Boy drives Dead Reckoning around, crushing most of the zombies around them. Slack then tells Riley to jump up on the roof, and he does, narrowly missing the clutches of zombies. They cross the bridge to get to the city, but they don't see a legless zombie is still holding onto the vehicle on the back.
Kaufman gets out of his car and looks around for Big Daddy. He gets out a reserve set of car keys from his bag and plans to drive way himself. Instead, Cholo comes from the shadows and pulls out his spear gun. He misses Kaufman, and is subsequently shot in the chest. He doesn't go down. Kaufman shoots him in the leg. Nothing. He shoots him in the shoulder. Cholo slowly slumps to the ground. While Kaufman is not looking, Cholo gets back up and attacks him. Kaufman is out of bullets, and Cholo is a zombie. Before Cholo can tear out his throat, Big Daddy returns with a propane tank on fire. He rolls it to the car and because it is drenched in gasoline, it explodes, killing both the zombie Cholo and Kaufman. Big Daddy is happy.
Dead Reckoning finally reaches the city, but they only find zombies eating people. It seems like there are no survivors in the city. Riley orders Charlie and Pretty Boy to fire the rockets at the zombies to destroy them. She does, and the zombies explode. When the smoke clears, Riley sees that nothing is moving. Everyone is dead. But then people slowly come out of hiding and walk towards Dead Reckoning. There are survivors. They plan on rebuilding the city slowly but surely. Riley still wants to leave for Canada.
Slack, Pretty Boy, Pillsbury, Charlie, and the two other people in Dead Reckoning agree and they plan on going with Riley. Riley sees Big Daddy once again through binoculars who is leading his zombies out of the city. He decides not to kill him, though, because the zombies are only looking for their own place to live, just like Riley and his friends are. The legless zombie on the back of the vehicle jumps a crew member, but Pillsbury manages to kill the zombie. Riley and his crew take off for Canada in Dead Reckoning and fire fireworks in the sky, since they won't be needing them anymore.